Synovial macrophage depletion with clodronate‐containing liposomes in rheumatoid arthritis

Barrera, Pilar; Blom, A.B.; Lent, P.L.E.M. van; Bloois, Louis van; Beijnen, Jos H.; Rooijen, Nico van; Malefijt, M.C. de Waal; Putte, L.B.A. van de; Storm, Gert; Berg, Wim B. van den

doi:10.1002/1529-0131(200009)43:9<1951::aid-anr5>3.0.co;2-k

Cited by 197 publications

(106 citation statements)

References 48 publications

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“…Stimulation of Fc␥RII/Fc␥RIII expressed by synovial intima cells may regulate proinflammatory cytokine production in the subintima. This is consistent with earlier studies in which it was shown that selective removal of intima cells from the RA joint by clodronate liposome treatment down-regulates TNF␣ in the subintima (57).…”

Section: Discussionsupporting

confidence: 93%

Increased expression of Fcγ receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor α and matrix metalloproteinase

Blom¹,

Radstake²,

Holthuysen³

et al. 2003

Arthritis & Rheumatism

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Objective. To evaluate Fc␥ receptor (Fc␥R) expression on synovial macrophages from rheumatoid arthritis (RA) patients and to determine whether this expression correlates with the production of the proinflammatory cytokines tumor necrosis factor ␣ (TNF␣), interleukin-1␤ (IL-1␤), IL-12, and matrix metalloproteinase 1 (MMP-1). We also sought to determine whether mature macrophages from RA patients express aberrant levels of Fc␥RI, Fc␥RII, and Fc␥RIII, and to determine the production of inflammatory mediators after immune complex (IC) stimulation.Methods. Immunohistochemistry was performed on cryostat sections of synovial biopsy specimens obtained from 27 RA patients and 5 controls. Fc␥R I, II, and III were detected, as well as the proinflammatory mediators IL-1, TNF␣, IL-12, and MMP-1. Monocytes were isolated from the blood of 10 RA patients and 10 healthy controls and cultured for 7 days with macrophage colony-stimulating factor to obtain macrophages. Using fluorescence-activated cell sorting, the expression of Fc␥RI, Fc␥RII, and Fc␥RIII was determined. On day 7, macrophages were stimulated with heat-aggregated gamma globulins (HAGGs) for 24 hours. Production of cytokines was measured using enzyme-linked immunosorbent assay, and production of gelatinases/ collagenases was measured by degradation of fluorescent gelatin.Results. Immunohistochemistry showed higher Fc␥RII and Fc␥RIII expression in RA synovium than in controls. Fc␥RII and Fc␥RIII, but not Fc␥RI, were highly correlated with the number of synovial macrophages. Consistent with this, TNF␣ expression correlated positively with Fc␥RIII expression. Moreover, MMP-1 expression strongly correlated with Fc␥R I, II, and III expression. Mature macrophages from RA patients showed significantly enhanced expression of Fc␥RII and Fc␥RIII compared with controls. Twentyfour hours after stimulation of RA macrophages with HAGGs, significantly higher production of TNF␣ and gelatinase/collagenase was measured.Conclusion. RA synovium and mature RA macrophages express significantly elevated levels of Fc␥RII and Fc␥RIII, resulting in much higher production of TNF␣ and gelatinase/collagenase after IC stimulation. These data suggest that disturbed expression of Fc␥R on mature synovial macrophages is involved in the pathology of RA.

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Section: Discussionsupporting

confidence: 93%

Increased expression of Fcγ receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor α and matrix metalloproteinase

Blom¹,

Radstake²,

Holthuysen³

et al. 2003

Arthritis & Rheumatism

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“…Increased numbers of macrophages, which can be activated to produce mediators of inflammation, are a prominent feature of inflammatory lesions, in particular those of a chronic nature (4), and their depletion from inflamed tissue (5) and from the circulation (6) can have profound benefit. With regard to RA, it has been observed that the number of macrophages in the synovial tissue correlates with the degree of joint erosion (7,8), and that increased numbers of macrophages are an early hallmark of active disease (9,10).…”

Section: Synovial Macrophage Number As An Ra Biomarkermentioning

confidence: 99%

The dynamics of macrophage lineage populations in inflammatory and autoimmune diseases

Hamilton¹,

Tak²

2009

Arthritis & Rheumatism

195

183

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“…administration of liposomeencapsulated dichloromethylene-bisphosphonate (clodronate liposomes). Clodronate liposomes have been used to study the role of macrophages in a number of chronic diseases (60,61). Clodronate is a cytotoxic compound that induces apoptotic cell death of macrophages when it is delivered encapsulated in a phospholipid bilayer liposome.…”

mentioning

confidence: 99%

Macrophage Depletion Abates Porphyromonas gingivalis–Induced Alveolar Bone Resorption in Mice

Lam

O'Brien-Simpson

Lenzo

et al. 2014

The Journal of Immunology

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114

140

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The role of the macrophage in the immunopathology of periodontitis has not been well defined. In this study, we show that intraoral inoculation of mice with Porphyromonas gingivalis resulted in infection, alveolar bone resorption, and a significant increase in F4/80+ macrophages in gingival and submandibular lymph node tissues. Macrophage depletion using clodronate-liposomes resulted in a significant reduction in F4/80+ macrophage infiltration of gingival and submandibular lymph node tissues and significantly (p < 0.01) less P. gingivalis–induced bone resorption compared with controls in BALB/c and C57BL/6 mice. In both mouse strains, the P. gingivalis–specific IgG Ab subclass and serum cytokine [IL-4, IL-10, IFN-γ, and IL-12 (p70)] responses were significantly (p < 0.01) lower in the macrophage-depleted groups. Macrophage depletion resulted in a significant reduction in the level of P. gingivalis infection, and the level of P. gingivalis infection was significantly correlated with the level of alveolar bone resorption. M1 macrophages (CD86+), rather than M2 macrophages (CD206+), were the dominant macrophage phenotype of the gingival infiltrate in response to P. gingivalis infection. P. gingivalis induced a significant (p < 0.01) increase in NO production and a small increase in urea concentration, as well as a significant increase in the secretion of IL-1β, IL-6, IL-10, IL-12 (p70), eotaxin, G-CSF, GM-CSF, macrophage chemoattractant protein-1, macrophage inflammatory protein-α and -β, and TNF-α in isolated murine macrophages. In conclusion, P. gingivalis infection induced infiltration of functional/inflammatory M1 macrophages into gingival tissue and alveolar bone resorption. Macrophage depletion reduced P. gingivalis infection and alveolar bone resorption by modulating the host immune response.

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Synovial macrophage depletion with clodronate‐containing liposomes in rheumatoid arthritis

Cited by 197 publications

References 48 publications

Increased expression of Fcγ receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor α and matrix metalloproteinase

Increased expression of Fcγ receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor α and matrix metalloproteinase

The dynamics of macrophage lineage populations in inflammatory and autoimmune diseases

Macrophage Depletion Abates Porphyromonas gingivalis–Induced Alveolar Bone Resorption in Mice

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